Yan Zhong-hai, Zhou Yi-ye, Fu Jing, Jiao Fei, Zhao Lei-wen, Guan Peng-fei, Huang Shu-zhen, Zeng Yi-tao, Zeng Fanyi
Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, PR China.
BMC Dev Biol. 2010 Mar 19;10:31. doi: 10.1186/1471-213X-10-31.
The interaction between the karyoplast and cytoplast plays an important role in the efficiency of somatic cell nuclear transfer (SCNT), but the underlying mechanism remains unclear. It is generally accepted that in nuclear transfer embryos, the reprogramming of gene expression is induced by epigenetic mechanisms and does not involve modifications of DNA sequences. In cattle, oocytes with various mitochondrial DNA (mtDNA) haplotypes usually have different ATP content and can further affect the efficiency of in vitro production of embryos. As mtDNA comes from the recipient oocyte during SCNT and is regulated by genes in the donor nucleus, it is a perfect model to investigate the interaction between donor nuclei and host oocytes in SCNT.
We investigated whether the in vitro development of reconstructed bovine embryos produced by SCNT would be influenced by mtDNA haplotype compatibility between the oocytes and donor cells. Embryos from homotype A-A or B-B showed significantly higher developmental ability at blastocyst stages than the heterotype A-B or B-A combinations. Post-implantation development ability, pregnancy rate up to day 90 of gestation, as well as percent of term births were higher in the homotype SCNT groups than in the heterotype groups. In addition, homotype and heterotype SCNT embryos showed different methylation patterns of histone 3-lysine 9 (H3K9) genome-wide and at pluripotency-related genes (Oct-4, Sox-2, Nanog).
Both histone and DNA methylation show that homotype SCNT blastocysts have a more successful epigenetic asymmetry pattern than heterotype SCNT blastocysts, which indicates more complete nuclear reprogramming. This may result from variability in their epigenetic patterns and responses to nuclear reprogramming. This suggests that the compatibility of mtDNA haplotypes between donor cells and host oocytes can significantly affect the developmental competence of reconstructed embryos in SCNT, and may include an epigenetic mechanism.
核质体与胞质体之间的相互作用在体细胞核移植（SCNT）效率中起着重要作用，但其潜在机制仍不清楚。人们普遍认为，在核移植胚胎中，基因表达的重编程是由表观遗传机制诱导的，不涉及DNA序列的修饰。在牛中，具有不同线粒体DNA（mtDNA）单倍型的卵母细胞通常具有不同的ATP含量，并会进一步影响胚胎体外生产的效率。由于在SCNT过程中mtDNA来自受体卵母细胞并受供体细胞核中的基因调控，因此它是研究SCNT中供体细胞核与宿主卵母细胞之间相互作用的理想模型。
我们研究了SCNT产生的重构牛胚胎的体外发育是否会受到卵母细胞与供体细胞之间mtDNA单倍型相容性的影响。同型A - A或B - B的胚胎在囊胚阶段的发育能力明显高于异型A - B或B - A组合。同型SCNT组的植入后发育能力、妊娠至第90天的妊娠率以及足月分娩率均高于异型组。此外，同型和异型SCNT胚胎在全基因组范围以及多能性相关基因（Oct - 4、Sox - 2、Nanog）处的组蛋白3 - 赖氨酸9（H3K9）甲基化模式不同。
组蛋白和DNA甲基化均表明，同型SCNT囊胚比异型SCNT囊胚具有更成功的表观遗传不对称模式，这表明核重编程更完整。这可能是由于它们表观遗传模式和对核重编程反应的变异性所致。这表明供体细胞与宿主卵母细胞之间mtDNA单倍型的相容性可显著影响SCNT中重构胚胎的发育能力，并且可能涉及一种表观遗传机制。
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